Is ECEL1 p.Arg702Leu (c.2105G>T) pathogenic?

ECEL1 p.Arg702Leu (c.2105G>T) is classified Conflicting classifications of pathogenicity in ECEL1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2024-11-26). AlphaMissense: likely benign (0.1178); Rare (popmax 0.436%, nfe).

How common is ECEL1 p.Arg702Leu (c.2105G>T) in the general population?

ECEL1 p.Arg702Leu (c.2105G>T) is rare (popmax 0.436%, nfe) (gnomAD).

What do computational predictors say about ECEL1 p.Arg702Leu (c.2105G>T)?

AlphaMissense predicts likely benign (score 0.1178) — an in-silico prediction, not a clinical call.

ECEL1 p.Arg702Leu

c.2105G>T · rs117012322 · VCV624184

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1178 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.436%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1178	likely benign
REVEL	0.406	indeterminate
SaProt	LLR -6.13	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.8	GERP 3.7, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 6,497 bp · p 0.15 · regional, not allelic
Overall
CADD	25.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.436% European (non-Finnish) · 5,139/1,180,006 alleles

Filtering AF 0.426% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.421%

Overall 0.368% 5,939/1,614,116 alleles · rare exomes 5,524/1,461,772 · genomes 415/152,344 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.436%	230
Remaining individualsnot grpmax-eligible	0.352%	284
South Asian	0.35%	286
Admixed American	0.298%	335
Middle Eastern	0.231%	433
Amishnot grpmax-eligible	0.11%	912
African / African-American	0.052%	1,925
Finnishnot grpmax-eligible	0.0375%	2,666
Ashkenazi Jewishnot grpmax-eligible	0.0135%	7,401

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: ECEL1
Protein: p.Arg702Leu
Coding: c.2105G>T
MANE Select: NM_004826
dbSNP: rs117012322
Type: single nucleotide variant
Location: chr2:232480764 (GRCh38)
Gene constraint: LOEUF 1.099 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.62
Residue 702: the peptidase m13 domain

Full ECEL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ECEL1 p.Arg702Gln Benign/Likely benign ★★ same residue
ECEL1 p.Arg702Trp Uncertain significance ★ ⚠ same residue
ECEL1 c.1685+1G>A Pathogenic ★★ same type
ECEL1 c.2151+2T>C Likely pathogenic ★★ same type
ECEL1 c.966+1G>A Pathogenic ★★ same type
ECEL1 p.Ala675Thr Pathogenic ★★ same type
ECEL1 p.Arg333Ter Pathogenic ★★ same type
ECEL1 p.Arg395Gln Pathogenic/Likely pathogenic ★★ ⚠ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/ecel1-p-arg702leu (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown